Skip to main content

Main menu

  • HOME
  • LATEST ARTICLES
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • RESOURCES
    • About BJGP Open
    • BJGP Open Accessibility Statement
    • Editorial Board
    • Editorial Fellowships
    • Audio Abstracts
    • eLetters
    • Alerts
    • Outreach
    • BJGP Life
    • Research into Publication Science
    • Advertising
    • Contact
    • Top 10 Research Articles of the Year
  • SPECIAL ISSUES
    • Special issue: Telehealth
    • Special issue: Race and Racism in Primary Care
    • Special issue: COVID-19 and Primary Care
    • Past research calls
  • CONFERENCE
  • RCGP
    • British Journal of General Practice
    • BJGP for RCGP members
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers

User menu

  • Alerts

Search

  • Advanced search
Intended for Healthcare Professionals
BJGP Open
  • RCGP
    • British Journal of General Practice
    • BJGP for RCGP members
    • RCGP eLearning
    • InnovAIT Journal
    • Jobs and careers
  • Subscriptions
  • Alerts
  • Log in
  • Follow bjgp on Twitter
  • Visit bjgp on Facebook
  • Blog
BJGP Open
Intended for Healthcare Professionals

Advanced Search

  • HOME
  • LATEST ARTICLES
  • ALL ISSUES
  • AUTHORS & REVIEWERS
  • RESOURCES
    • About BJGP Open
    • BJGP Open Accessibility Statement
    • Editorial Board
    • Editorial Fellowships
    • Audio Abstracts
    • eLetters
    • Alerts
    • Outreach
    • BJGP Life
    • Research into Publication Science
    • Advertising
    • Contact
    • Top 10 Research Articles of the Year
  • SPECIAL ISSUES
    • Special issue: Telehealth
    • Special issue: Race and Racism in Primary Care
    • Special issue: COVID-19 and Primary Care
    • Past research calls
  • CONFERENCE
Research

Concerns regarding tablet splitting: a systematic review

Aanchal K Saran, Natalie A Holden and Scott R Garrison
BJGP Open 2022; 6 (3): BJGPO.2022.0001. DOI: https://doi.org/10.3399/BJGPO.2022.0001
Aanchal K Saran
1 Department of Family Medicine, University of Alberta, Edmonton, Alberta, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: aanchalp@ualberta.ca
Natalie A Holden
2 Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott R Garrison
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info
  • eLetters
  • PDF
Loading

Abstract

Background Tablet splitting can provide dose flexibility and cost savings; however, pharmaceutical representatives typically discourage the practice.

Aim To identify and summarise all published concerns related to tablet splitting and to present the experimental evidence that investigates those concerns.

Design & setting Systematic review and qualitative synthesis of tablet-splitting concerns and evidence.

Method Medline and EMBASE databases were searched over all years of publication for articles in English discussing the splitting of tablets. Eligible articles included original research, narrative reviews, systematic reviews, and expert opinion.

Results After removing duplicates, 1837 potentially relevant articles underwent dual review, whereupon 1612 articles were excluded based on title and abstract. After examination of 225 full texts, 138 articles were included (one systematic review, four narrative reviews, 101 original research articles, and 32 opinion articles). The described concerns included difficulty breaking tablets, loss of mass, weight variability, chemical instability, overly rapid dosing if sustained-release medications are split, non-compliance, and patient confusion resulting in medication errors. No substantive evidence was found to support concerns regarding loss of mass, weight variability, chemical instability, or non-compliance. Evidence does support some older adults struggling to split tablets without tablet splitters, and the inappropriateness of splitting sustained-release preparations, given the potential for alteration of the rate of drug release for some products.

Conclusion With the exception of sustained-release tablets, which should not be split, and excepting those older people who may struggle to split tablets based on physical limitations, there is little evidence to support tablet-splitting concerns.

  • cost savings
  • delayed-action preparations
  • dose-reduction
  • geriatric prescribing
  • medication errors
  • pill-splitting
  • tablets

How this fits in

In the authors’ experience, pharmaceutical representatives commonly discourage the splitting of their products. In the literature, concerns have been raised about difficulty breaking tablets, losing tablet mass, unequal splitting, chemical instability, confusion leading to medication errors, and the mistaken splitting of sustained-release preparations. Although some older adults may struggle to split tablets without tablet splitters, little evidence was found to justify tablet-splitting concerns other than the need to avoid splitting sustained-release preparations. With the exception of sustained-release medications, tablet splitting to facilitate lower medication doses and lower medication costs appears safe.

Introduction

Using the lowest effective dose of all medications is key to minimising adverse drug effects in older adults and those with polypharmacy.1,2 Splitting tablets in half can help to achieve these lower doses, and often results in substantial cost savings for patients.3–5 However, manufacturers commonly discourage the splitting of their products, and this leads some healthcare providers to be reluctant to suggest it.6 To obtain more objective information on the safety of tablet splitting, a systematic review of the literature was conducted in which all arguments against tablet splitting, and all original research that validated or refuted those concerns, were gathered and synthesised.

Method

Review process

Dual reviewers were employed to evaluate titles and abstracts. A single reviewer assessed full texts for inclusion and extracted information. Two authors discussed and synthesised the data. As the primary interest was in gathering and synthesising both opinion and non-clinical trial research related to tablet splitting, the usual PRISMA processes for evaluating study quality (which focus on clinical trials) did not apply.

Databases and search criteria

On 29 May 2019, Medline and EMBASE databases were searched for eligible studies spanning all available years of publication. With the assistance of a medical librarian searches were developed (see Supplementary Appendix S1) centred on the concepts of tablet (tablet*, pill, pills, and capsule) and splitting (split*, half, halv*, divid*, break*, cut, and cutting). The search was expanded under the heading of ’exp Tablets/ad [Administration & Dosage]’ and limited to the English language.

Included studies

All studies discussing tablet splitting were obtained and read. This included original research, expert opinion, narrative review, and systematic review. Studies were excluded if tablet splitting was not a major focus of the article or if the article was not written in the English language.

Results

The database search yielded a total of 2425 articles, of which 588 were duplicates. After duplicates were removed, 1837 titles and abstracts were screened for inclusion. The full texts of 225 articles were examined, of which 138 met the inclusion criteria;1–138 these were included in the qualitative review (Figure 1). The characteristics of included publications are provided in Table 1. The list of included articles is available in the online supplement (see Supplementary Appendix S2), as is a table breaking each study down according to publication type and the concerns raised or addressed (see Supplementary Table S1).

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1. Study flow diagram
View this table:
  • View inline
  • View popup
Table 1. Characteristics of included publications (n = 138)

Key concern 1: difficulty breaking tablets

Concern that patients may struggle to split tablets was raised in 38 articles,1,3,5,7,8,11,14,16,27,34,39,43,46,50,51,54,72,91,92,95,98,99,103,105,107,108,110–113,120–122,124,125,128,134,135 and pertained to both splitting by hand and the use of a tablet splitter. This concern focused on older adults potentially being limited by diminished manual dexterity or visual or cognitive impairments.46,72,120 Authors assumed tablets were harder to split when smaller, harder, and asymmetric in shape,40 and that splitting was easier using a tablet splitter than by hand. Score lines were expected to make splitting easier.72

Evidence

Manual splitting

Of 120 older acute care patients admitted to a teaching hospital, 94 (78.3%) were unable to either break a scored tablet by hand unaided or to open a medication container manually.139 Manual splitting was similarly self-reported as being difficult by 29.7% of home-dwelling adults aged ≥70 years,140 and 36% of home-dwelling adults aged ≥75 years.141

Geometry and composition of the tablet matter

People who are diabetic aged >70 years were unable to split generic glyburide tablets 80% of the time, but only 30% failed to split a non-generic tablet with an easier to split design.142 Younger adults split tablets by hand more successfully than older adults (78.2% versus 38.1%), but age did not correlate with the accuracy of splitting tablets into equal halves when successfully split.72

Use of a tablet splitter

Numerous studies support tablet splitters making splitting easier.3,4,93 Of 233 responders to a survey (73% response rate) of Californian Air Force medical centre patients asked to split lovastatin tablets to reduce costs (mean age 65 years), only 6% felt the splitter was not easy to use.143 Similar results were reported for a convenience sample of 30 Dutch patients selected to have a wide variation in physical ability, and asked to split both a large and small round uncoated tablet. While 17% of all participants and 42% of those aged ≥65 years failed to split tablets by hand, all participants successfully split tablets using two types of splitter.144 In another convenience sample of 30 older adults (mean age 64.9 years), all successfully split a variety of tablets, although accurately splitting tablets into equal halves was better in those given instructions on splitter use.65 Overall, evidence suggests splitting tablets by hand is challenging for some older adults, for whom tablet splitters, or assistance from pharmacists or family may be needed.39

Key concern 2: loss of mass

Concern that splitting could pulverise (turn to powder) a meaningful proportion of the tablet was raised in 29 articles.1,2,9,13,28,29,31,34,43,46,50,57,72,74,77,81,82,92,101,110,118,121,122,124,125,128,133,134,137 The resulting loss of mass could potentially lead to incorrect dosage, and contamination/health concerns for those unwittingly exposed to the residue.72,121,128 If tablets fragment to a large degree they may even need to be discarded, leading to increased healthcare costs.64

Evidence

Although losses of mass up to 14% have been observed for tablets split into quarters,127 the average loss has been reported as 2.6% for round tablets, and as ‘insignificant‘ when tablets are oblong (an elongated oval shape).145 Multiple other studies describe loss of mass as acceptable or insignificant.4,35,79 Overall, evidence suggests that loss of mass is negligible for the vast majority of medications.

Key concern 3: chemical instability

Concern that split tablets would chemically or physically degrade was raised in 19 articles.5,21,26–28,36,39,42,50,52,54,70,79,82,83,98,103,118,128 Concerns centred on increased friability of split tablets, and chemical reaction with air, water, or light once coatings were breached or packaging was removed. Splitting drugs with an enteric coating, used as a protective barrier against stomach acidity, can also increase the rate of degradation within the gut.36,64,70,77,82 Potential consequences could include patients experiencing more adverse effects, or receiving lower effective doses of the active substance.35

Evidence

One study assessed chemical stability of 11 quartered cardiovascular medications stored in plastic containers without light exposure 30–45 days post-split. Three of these 11 medications demonstrated decreased levels of the active drug, including digoxin (for which mean drug concentration was 68% of expected), spironolactone (82%), and both generic and brand name amlodipine (91% and 93%, respectively). Only the drop in digoxin concentration was believed to be clinically important.83 Similarly, split tablets were considered chemically stable for levothyroxine (after 8 weeks at 25°C/60% relative humidity), aspirin (after 1 week of refrigeration), and gabapentin (after 9 weeks at room temperature).36,54,146 Another study found gabapentin, risperidone, and losartan to be chemically stable at 90 days (25°C ± 2°C/60% ± 5% relative humidity).147

More evidence on chemical stability of specific split medications is needed. However, of the 16 studied medications identified, only digoxin degraded fast enough for chemical instability to be considered clinically important. Where medications are known to degrade, or where there is uncertainty, splitting only one tablet at a time should mitigate this concern. No studies were found examining bioavailability after enteric coated tablets were split.

Key concern 4: weight/dose variability

Concern that tablets would split unequally, and hence vary in dosage, was raised in 93 articles. This could lead to underdosing or overdosing, and was of particular concern for drugs with a narrow therapeutic index.39,43

Evidence

Several studies evaluated split tablet weight variability.22,41,79,83,110 One study analysed 560 pharmacy-dispensed split tablets of 22 drugs, and found that only 32 (5.7%) of 560 tablet halves deviate >15% from the expected weight.44 In contrast, 41.3% of 1752 hydrochlorothiazide tablets manually split (that is, without a tablet splitter) by 94 healthy volunteers deviated from their expected weight by >10%.79 Other studies reported less clinically significant weight variation after splitting,35,66 including studies reporting the drug content of half-tablets of warfarin and salbutamol, split by tablet splitter, to fall within United States Pharmacopeia specification criteria.89,93 In a study of scored and unscored tablets of Risperdal, Paxil, and Zoloft split by tablet-splitter, all half-tablets produced uniform doses.73 Similarly, for 30 lorazepam half-tablets, drug content was within 75%–125% of expected for every half portion.22

Arguments against the clinical importance of weight variability, even where it does exist, were:

  • average doses remain the same over time;

  • differences in body weight are likely to have greater influence on drug levels than the observed minor differences in tablet weight;148 and

  • a 10% variation in a single dose will not mean a 10% variation in steady state drug levels, especially for drugs with longer half-lives.92,99

In terms of efficacy, multiple studies found no significant changes in total or low-density lipoprotein cholesterol levels after splitting statins.69,97,149 Overall, although minor weight variation is likely to occur to some extent, it is unlikely to be clinically important.

Key concern 5: sustained-release medications

Concern about splitting sustained-release medication was raised in 27 articles.12,16,54,64,74,76,77,79,81,84,88,90,93,96,98,99,102–105,113–117,121,122 Sustained release of medications with short half-lives is commonly achieved either by sustained-release external tablet coatings, or by embedding medication in a slowly degrading matrix. Splitting such preparations could compromise the release mechanism and result in overly rapid drug release and potential harm from overdose.6,84,88,150,151

Evidence

While sustained-release preparations are not intended for splitting, it has been explored in some studies. Altered drug-release kinetics were reported post-split for sustained-release matrix tablets of diltiazem116 and aspirin,84 but not melatonin — although further cutting into quarters or crushing melatonin matrix tablets did alter release kinetics.113 Film-coated verapamil tablets also retained their release characteristics after splitting.78 Overall, while some sustained-release medications may be safe to split, the impracticality of providers trying to remember which products can be split and which cannot, and the potential harm of overly rapid drug release, supports the generalisation against splitting all slow-release products.152

Key concern 6: confusion/non-compliance

Concern that directions to split tablets add complications that might confuse patients or lead to non-compliance was raised in 24 articles.1,3,5,6,11,31,39,43,50,51,74,77,81,95,98,99,110–112,121,124,128,133,137 In particular, there was concern that patients could split the wrong medication, that splitting could lead to miscommunication with patients or pharmacists (such as 1/2 tablet being misinterpreted to mean 1–2 tablets), or that the extra hurdle to use the medication could lead some to stop it altogether.

Evidence

Using tablet counting and patient questionnaires, and tracking the patient refill history of 105 fosinopril users, there was no significant difference in compliance for those who split fosinopril tablets, and those who did not.101 This is consistent with reporting from a tablet-splitting programme, which reported no compliance problems.143 Another tablet-splitting programme involving 2019 patients reported that only 7% of patients found tablet splitting to influence their desire to take medication.97 No studies examining the frequency of errors being made by patients or pharmacists were found.

Overall, while evidence is needed to explore whether confusion or miscommunication can lead to medication errors, available evidence suggests compliance does not suffer when tablets are split. For patients where confusion may be more likely, this problem may be overcome by bubble-packing by pharmacists or weekly dosette box preparation by caregivers.

Discussion

Summary

Concerns related to tablet splitting include difficulty breaking tablets, loss of mass, weight/dose variability, chemical instability, disruption of sustained-release mechanisms, and confusion/non-compliance. Of these, evidence supports only the concern that some frail older adults may struggle to split tablets without a tablet splitter, and the caution that sustained-release tablets should not be split.

Strengths and limitations

This study’s findings are strengthened by its having reviewed the literature systematically, with the use of dual reviewers in the review of titles and abstracts. It is limited by the qualitative nature of the synthesis, and the observational nature of much of the evidence. While including essentially all article types is a strength insofar as it enables a broad perspective of the topic, it is also a limitation, in that the tools and templates for reporting a study’s methods, findings, quality, and bias do not lend themselves to a collection of included studies that range from opinion to basic science.

Comparison with existing literature

Taken together, the evidence gathered supports the experience of tablet-splitting programmes that describe splitting tablets as safe, effective, and readily accepted by patients and providers.5,97 The findings are at odds with narrative reviews that caution against tablet splitting.98

Implications for practice

Provided that patients who would struggle to split tablets are assisted in doing so, and provided that sustained-release tablets are not targeted for splitting, tablet splitting appears to be an effective tool for utilising minimum effective doses and reducing medication costs.

Notes

Funding

This study received funding in the form of a grant from the Northern Alberta Family Medicine Fund (Department of Family Medicine, University of Alberta).

Provenance

Freely submitted; externally peer reviewed.

Ethical approval

Not applicable.

Acknowledgements

The authors would like to thank Janice Kung, a Health Sciences Librarian at the University of Alberta, for her invaluable assistance in building the electronic title search.

Competing interests

The authors declare that no competing interests exist.

Disclosure

The authors report no conflicts of interest in this work

  • Received January 7, 2022.
  • Revision received January 7, 2022.
  • Accepted January 31, 2022.
  • Copyright © 2022, The Authors

This article is Open Access: CC BY license (https://creativecommons.org/licenses/by/4.0/)

References

  1. 1.↵
    1. Cohen JS
    (2002) Tablet splitting: imperfect perhaps, but better than excessive dosing. J Am Pharm Assoc (Wash) 42 (2):160–162, doi:10.1331/108658002763508443, pmid:11926659.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Morreale A
    (2011) Pill-splitting: correctly used, it can benefit patients and serve society. Drug Topics 155 (8). 14.
  3. 3.↵
    1. Cohen CI,
    2. Cohen SI
    (2000) Potential cost savings from pill splitting of newer psychotropic medications. Psychiatr Serv 51 (4):527–529, doi:10.1176/appi.ps.51.4.527, pmid:10737832.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Fahelelbom KMS,
    2. Al-Tabakha MMM,
    3. Eissa NAM,
    4. Javadi J
    (2016) Evaluation of certain pharmaceutical quality attributes of lisinopril split tablets. Sci Pharm 84 (4):646–653, doi:10.3390/scipharm84040646, pmid:27727195.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Carey H,
    2. Fondriest M
    (2017) Cost-savings from an antipsychotic tablet-splitting program. P T 42 (6):384–393, pmid:28579725.
    OpenUrlPubMed
  6. 6.↵
    1. Navarro RP
    (2009) Tablet splitting: much ado about nothing? J Manag Care Pharm 15 (3):272–274, doi:10.18553/jmcp.2009.15.3.272, pmid:19326958.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Green G,
    2. Berg C,
    3. Polli JE,
    4. Barends DM
    (2010) Pharmacopeial standards for the subdivision characteristics of scored tablets. Pharma Times 42 (9):1598–1612.
    OpenUrl
  8. 8.↵
    1. de Lima Moreira F,
    2. de Oliveira Silva E,
    3. Bonfilio R,
    4. et al.
    (2013) Evaluation of the influence of splitting on content uniformity of captopril tablets. Curr Pharm Anal 9 (2):139–144.
    OpenUrl
  9. 9.↵
    (2008) Splitting tablets challenges you and your patients. Alta RN 64 (7):24–25, pmid:18942487.
    OpenUrlPubMed
  10. 10.
    (2002) Splitting pills OK in certain cases. Health News 8 (11):9, pmid:12523256.
    OpenUrlPubMed
  11. 11.↵
    (2004) Tablet splitting: evaluating appropriateness for patients. J Am Pharm Assoc (2003) 44 (3):324–325, doi:10.1331/154434504323063959, pmid:15191242.
    OpenUrlCrossRefPubMed
  12. 12.↵
    (2014) Tablet splitting. JAMA 311 (5):521, doi:10.1001/jama.2014.208, pmid:24496538.
    OpenUrlCrossRefPubMed
  13. 13.↵
    (2012) Tablet splitting. Med Lett Drugs Ther 54 (1396), pmid:22869291. 63.
    OpenUrlPubMed
  14. 14.↵
    (2009) Tablet splitting. Med Lett Drugs Ther 51 (1318):62–63, pmid:19661854.
    OpenUrlPubMed
  15. 15.
    (2002) Pill splitting cuts rx costs but can pose medical risks. Pa Health You 105 (3):13, pmid:12373793.
    OpenUrlPubMed
  16. 16.↵
    (2008) Pill splitting. Harv Mens Health Watch 13 (4):7, pmid:19024770.
    OpenUrlPubMed
  17. 17.
    1. Webster RT
    (2002) Pill splitting. Am J Manag Care 8 (11), pmid:12437308. 925.
    OpenUrlPubMed
  18. 18.
    (2004) One on one. is it OK for me to split my prescription drug tablets to save money? Mayo Clin Womens Healthsource 8 (10):8, pmid:15505577.
    OpenUrlPubMed
  19. 19.
    (2008) Is it safe to split my pills? Johns Hopkins Med Lett Health After 50 20 (10), pmid:19927394. 8.
    OpenUrlPubMed
  20. 20.
    (2002) Is it OK for me to split my pills to save money on medications? Johns Hopkins Med Lett Health After 50 14 (10), pmid:12523263. 8.
    OpenUrlPubMed
  21. 21.↵
    (2002) Health tips. splitting pills. Mayo Clin Health Lett 20 (5):3, pmid:16134246.
    OpenUrlPubMed
  22. 22.↵
    1. Zaid AN,
    2. Al-Ramahi RJ,
    3. Ghoush AA,
    4. et al.
    (2013) Weight and content uniformity of lorazepam half-tablets: A study of correlation of A low drug content product. Saudi Pharm J 21 (1):71–75, doi:10.1016/j.jsps.2011.12.009, pmid:23960821.
    OpenUrlCrossRefPubMed
  23. 23.
    1. Zaid AN,
    2. Ghoush AA,
    3. Al-Ramahi R,
    4. Are’r M
    (2012) Evaluation of the discrepancy between the european pharmacopoeia test and an adopted united states pharmacopoeia test regarding the weight uniformity of scored tablet halves: is harmonization required? PDA J Pharm Sci Technol 66 (1):20–27, doi:10.5731/pdajpst.2012.00791, pmid:22307659.
    OpenUrlAbstract/FREE Full Text
  24. 24.
    1. Zaid AN,
    2. Al-Ramahi R,
    3. Ghoush AA,
    4. et al.
    (2012) Influence of physical factors on tablet splitting, weight and content uniformity of atenolol tablets. J Pharm Investig 42 (5):229–234, doi:10.1007/s40005-012-0030-7.
    OpenUrlCrossRef
  25. 25.
    1. Zaid AN,
    2. Ghosh AA
    (2011) Compliance of scored tablet halves produced by palestinian pharmaceutical companies with the new european pharmacopoeia requirements. Arch Pharm Res 34 (7):1183–1189, doi:10.1007/s12272-011-0717-8, pmid:21811926.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Zaid AN,
    2. Abu GA,
    3. Kittana N
    (2010) Weight uniformity of scored tablet halves manufactured by palestinian pharmaceutical companies. Int J Pharm Compd 14 (3):257–260, pmid:23965504.
    OpenUrlPubMed
  27. 27.↵
    1. Reddy VY,
    2. Venkatesh MP,
    3. Kumar TMP
    (2014) Tablet scoring and its regulatory perspective. Applied Clinical Research, Clinical Trials and Regulatory Affairs 1 (2):107–110, doi:10.2174/2213476X01666141107192108.
    OpenUrlCrossRef
  28. 28.↵
    1. Wójcik-Pastuszka D,
    2. Juszkiewicz K,
    3. Özhan G,
    4. Musiał W
    (2018) Influence of tablet splitting on dissolution of tablets with naproxen sodium. Dissolution Technologies 25 (2):16–23, doi:10.14227/DT250218P16.
    OpenUrlCrossRef
  29. 29.↵
    1. Wójcik-Pastuszka D,
    2. Biedrawa AM,
    3. Haznar-Garbacz D,
    4. Musiał WS
    (2018) The influence of physical division of tablets on the variability of release kinetics of gliclazide. Monatsh Chem 149 (5):953–959, doi:10.1007/s00706-018-2176-0, pmid:29720769.
    OpenUrlCrossRefPubMed
  30. 30.
    1. Wilczyński S,
    2. Koprowski R,
    3. Duda P,
    4. et al.
    (2016) Microtomographic studies of subdivision of modified-release tablets. Int J Pharm 511 (2):899–912, doi:10.1016/j.ijpharm.2016.07.069, pmid:27480395.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Weissman EM,
    2. Dellenbaugh C
    (2007) Impact of splitting risperidone tablets on medication adherence and on clinical outcomes for patients with schizophrenia. Psychiatr Serv 58 (2):201–206, doi:10.1176/ps.2007.58.2.201, pmid:17287376.
    OpenUrlCrossRefPubMed
  32. 32.
    1. Weiss GG
    (2006) What would you do? splitting pills. Med Econ 83 (20), pmid:17128727. 70.
    OpenUrlPubMed
  33. 33.
    1. Vuchetich PJ,
    2. Garis RI,
    3. Jorgensen AMD
    (2003) Evaluation of cost savings to a state medicaid program following a sertraline tablet-splitting program. J Am Pharm Assoc (2003) 43 (4):497–502, doi:10.1331/154434503322226248, pmid:12952314.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Vranić E,
    2. Uzunović A
    (2008) Comparison of some physical parameters of whole and scored lisinopril and lisinopril/hydrochlorthiazide tablets. Bosn J Basic Med Sci 8 (4):391–395, doi:10.17305/bjbms.2008.2906, pmid:19125715.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Vranić E,
    2. Uzunović A
    (2007) Influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Bosn J Basic Med Sci 7 (4):328–334, doi:10.17305/bjbms.2007.3022, pmid:18039191.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Volpe DA,
    2. Gupta A,
    3. Ciavarella AB,
    4. et al.
    (2008) Comparison of the stability of split and intact gabapentin tablets. Int J Pharm 350 (1–2):65–69, doi:10.1016/j.ijpharm.2007.08.041, pmid:17935918.
    OpenUrlCrossRefPubMed
  37. 37.
    1. Verrue C,
    2. Mehuys E,
    3. Boussery K,
    4. et al.
    (2011) Tablet-splitting: a common yet not so innocent practice. J Adv Nurs 67 (1):26–32, doi:10.1111/j.1365-2648.2010.05477.x, pmid:21158902.
    OpenUrlCrossRefPubMed
  38. 38.
    1. Van Vooren L,
    2. De Spiegeleer B,
    3. Thonissen T,
    4. et al.
    (2002) Statistical analysis of tablet breakability methods. J Pharm Pharm Sci 5 (2):190–198, pmid:12207873.
    OpenUrlPubMed
  39. 39.↵
    1. van Santen E,
    2. Barends DM,
    3. Frijlink HW
    (2002) Breaking of scored tablets: a review. Eur J Pharm Biopharm 53 (2):139–145, doi:10.1016/s0939-6411(01)00228-4, pmid:11879995.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Van der Steen KC,
    2. Frijlink HW,
    3. Schipper CMA,
    4. Barends DM
    (2010) Prediction of the ease of subdivision of scored tablets from their physical parameters. AAPS PharmSciTech 11 (1):126–132, doi:10.1208/s12249-009-9365-4, pmid:20077042.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Teng J,
    2. Song CK,
    3. Williams RL,
    4. Polli JE
    (2002) Lack of medication dose uniformity in commonly split tablets. J Am Pharm Assoc (Wash) 42 (2):195–199, doi:10.1331/108658002763508489, pmid:11926662.
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Teixeira MT,
    2. Sá-Barreto LCL,
    3. Gratieri T,
    4. et al.
    (2017) Key technical aspects influencing the accuracy of tablet subdivision. AAPS PharmSciTech 18 (4):1393–1401, doi:10.1208/s12249-016-0615-y, pmid:27586963.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Tahaineh LM,
    2. Gharaibeh SF
    (2012) Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice. J Pharm Pract 25 (4):471–476, doi:10.1177/0897190012442716, pmid:22544621.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Rosenberg JM,
    2. Nathan JP,
    3. Plakogiannis F
    (2002) Weight variability of pharmacist-dispensed split tablets. J Am Pharm Assoc (Wash) 42 (2):200–205, doi:10.1331/108658002763508498, pmid:11926663.
    OpenUrlCrossRefPubMed
  45. 45.
    1. Rodenhuis N,
    2. De Smet PAGM,
    3. Barends DM
    (2004) The rationale of scored tablets as dosage form. Eur J Pharm Sci 21 (2–3):305–308, doi:10.1016/j.ejps.2003.10.018, pmid:14757502.
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Rodenhuis N,
    2. de Smet PA,
    3. Barends DM
    (2003) Patient experiences with the performance of tablet score lines needed for dosing. Pharm World Sci 25 (4):173–176, doi:10.1023/a:1024852529628, pmid:12964497.
    OpenUrlCrossRefPubMed
  47. 47.
    1. Radebaugh GW,
    2. DeMuth JE,
    3. Parr AF,
    4. et al.
    (2013) A new general chapter on tablet splitting. Pharmacopeial Forum 39 (4).
  48. 48.
    1. Stimpel M,
    2. Vetter H,
    3. Küffer B,
    4. et al.
    (1985) The scored tablet--a source of error in drug dosing? J Hypertens Suppl 3 (1):S97–S99, pmid:3870476.
    OpenUrlCrossRefPubMed
  49. 49.
    1. Stimpel M,
    2. Küffer B,
    3. Groth H,
    4. Vetter W
    (1984) Breaking tablets in half. Lancet 1 (8389):1299, doi:10.1016/s0140-6736(84)92481-4, pmid:6145006.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Stafford RS,
    2. Radley DC
    (2002) The potential of pill splitting to achieve cost savings. Am J Manag Care 8 (8):706–712, pmid:12212758.
    OpenUrlPubMed
  51. 51.↵
    1. Somogyi O,
    2. Meskó A,
    3. Csorba L,
    4. et al.
    (2017) Pharmaceutical counselling about different types of tablet-splitting methods based on the results of weighing tests and mechanical development of splitting devices. Eur J Pharm Sci 106 262–273, doi:10.1016/j.ejps.2017.05.071, pmid:28606803.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Siderov J,
    2. Sivagnanam G
    (2003) Splitting tablets. Aust Prescr 26 (2):5–8.
    OpenUrl
  53. 53.
    1. Shao J,
    2. Polli JE
    (2007) Evaluation of a novel tablet splitter. J Am Pharm Assoc (2003) 47 (2):185–187, doi:10.1331/P427-7364-V258-9555, pmid:17510006.
    OpenUrlCrossRefPubMed
  54. 54.↵
    1. Shah RB,
    2. Collier JS,
    3. Sayeed VA,
    4. et al.
    (2010) Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium. AAPS PharmSciTech 11 (3):1359–1367, doi:10.1208/s12249-010-9515-8, pmid:20740332.
    OpenUrlCrossRefPubMed
  55. 55.
    1. Shah VP,
    2. Yamamoto LA,
    3. Schuirman D,
    4. et al.
    (1987) Analysis of in vitro dissolution of whole vs. half controlled-release theophylline tablets. Pharm Res 4 (5):416–419, doi:10.1023/a:1016442514205, pmid:3508552.
    OpenUrlCrossRefPubMed
  56. 56.
    1. Sedrati M,
    2. Arnaud P,
    3. Fontan JE,
    4. Brion F
    (1994) Splitting tablets in half. Am J Hosp Pharm 51 (4), pmid:8017428. 548, 550.
    OpenUrlPubMed
  57. 57.↵
    1. Schellhase EM,
    2. Hardin AK
    (2017) Development and implementation of a tablet splitting education program in a veterans affairs medical center. Hosp Pharm 38 (5):453–457, doi:10.1177/001857870303800513.
    OpenUrlCrossRef
  58. 58.
    1. Saseen J
    (2006) Splitting scored tablets is efficacious and safe, but cost savings are often limited. J Fam Pract 55 (8). 707.
  59. 59.
    1. Santos JMS
    (2012) Inability to swallow tablets is common and cause for concern. Nurs Times 108 (48), pmid:23488330. 11.
    OpenUrlPubMed
  60. 60.
    1. Sam K
    (2002) Tablet cutting. Int J Pharm Compd 6 (2):118–119, pmid:23982132.
    OpenUrlPubMed
  61. 61.
    1. Rashed SM,
    2. Nolly RJ,
    3. Robinson L,
    4. Thoma L
    (2017) Weight variability of scored and unscored split psychotropic drug tablets. Hosp Pharm 38 (10):930–934, doi:10.1177/001857870303801013.
    OpenUrlCrossRef
  62. 62.
    1. Quinzler R,
    2. Schmitt SPW,
    3. Pritsch M,
    4. et al.
    (2009) Substantial reduction of inappropriate tablet splitting with computerised decision support: a prospective intervention study assessing potential benefit and harm. BMC Med Inform Decis Mak 9 doi:10.1186/1472-6947-9-30, pmid:19523205. 30.
    OpenUrlCrossRefPubMed
  63. 63.
    1. Quinzler R,
    2. Szecsenyi J,
    3. Haefeli WE
    (2007) Tablet splitting: patients and physicians need better support. Eur J Clin Pharmacol 63 (12):1203–1204, doi:10.1007/s00228-007-0382-5, pmid:17899044.
    OpenUrlCrossRefPubMed
  64. 64.↵
    1. Quinzler R,
    2. Gasse C,
    3. Schneider A,
    4. et al.
    (2006) The frequency of inappropriate tablet splitting in primary care. Eur J Clin Pharmacol 62 (12):1065–1073, doi:10.1007/s00228-006-0202-3, pmid:17024485.
    OpenUrlCrossRefPubMed
  65. 65.↵
    1. Peek BT,
    2. Al-Achi A,
    3. Coombs SJ
    (2002) Accuracy of tablet splitting by elderly patients. JAMA 288 (4):451–452, doi:10.1001/jama.288.4.451, pmid:12132974.
    OpenUrlCrossRefPubMed
  66. 66.↵
    1. Polli JE,
    2. Kim S,
    3. Martin BR
    (2003) Weight uniformity of split tablets required by a veterans affairs policy. J Manag Care Pharm 9 (5):401–407, doi:10.18553/jmcp.2003.9.5.401, pmid:14613437.
    OpenUrlCrossRefPubMed
  67. 67.
    1. Polinski JM,
    2. Schneeweiss S,
    3. Maclure M,
    4. et al.
    (2011) Time series evaluation of an intervention to increase statin tablet splitting by general practitioners. Clin Ther 33 (2):235–243, doi:10.1016/j.clinthera.2011.02.009, pmid:21497707.
    OpenUrlCrossRefPubMed
  68. 68.
    1. Pereira GRS,
    2. Taveira SF,
    3. Cunha-Filho M,
    4. Marreto RN
    (2018) The effects of fillers and binders on the accuracy of tablet subdivision. AAPS PharmSciTech 19 (7):2929–2933, doi:10.1208/s12249-018-1144-7, pmid:30120694.
    OpenUrlCrossRefPubMed
  69. 69.↵
    1. Parra D,
    2. Beckey NP,
    3. Raval HS,
    4. et al.
    (2005) Effect of splitting simvastatin tablets for control of low-density lipoprotein cholesterol. Am J Cardiol 95 (12):1481–1483, doi:10.1016/j.amjcard.2005.02.019, pmid:15950578.
    OpenUrlCrossRefPubMed
  70. 70.↵
    1. Oberoi RK,
    2. Zhao W,
    3. Sidhu DS,
    4. et al.
    (2018) A phase 1 study to evaluate the effect of crushing, cutting into half, or grinding of glecaprevir/pibrentasvir tablets on exposures in healthy subjects. J Pharm Sci 107 (6):1724–1730, doi:10.1016/j.xphs.2018.02.015, pmid:29476763.
    OpenUrlCrossRefPubMed
  71. 71.
    1. Noviasky J,
    2. Lo V,
    3. Luft DD,
    4. Saseen J
    (2006) Clinical inquiries. which medications can be split without compromising efficacy and safety? J Fam Pract 55 (8):707–708, pmid:16882445.
    OpenUrlPubMed
  72. 72.↵
    1. Notenboom K,
    2. Vromans H,
    3. Schipper M,
    4. et al.
    (2016) Relationship between age and the ability to break scored tablets. Front Pharmacol 7 doi:10.3389/fphar.2016.00222, pmid:27507946. 222.
    OpenUrlCrossRefPubMed
  73. 73.↵
    1. Nolly RJ,
    2. Rodrigues P,
    3. Thoma L
    (2017) Weight variability of scored and unscored psychotropic drug tablets split by a uniquely designed tablet splitting device. Hosp Pharm 40 (4):321–325, doi:10.1177/001857870504000406.
    OpenUrlCrossRef
  74. 74.↵
    1. Nidanapu RP,
    2. Rajan S,
    3. Mahadevan S,
    4. Gitanjali B
    (2016) Tablet splitting of antiepileptic drugs in pediatric epilepsy: potential effect on plasma drug concentrations. Paediatr Drugs 18 (6):451–463, doi:10.1007/s40272-016-0193-1, pmid:27704404.
    OpenUrlCrossRefPubMed
  75. 75.
    1. Nichols E,
    2. Wiederkehr DP,
    3. Doyle J
    (2010) PSS34 the impact of potential pill splitting on generic and branded finasteride uptake. Value Health 13 (7), doi:10.1016/S1098-3015(11)72663-8. A404.
    OpenUrlCrossRef
  76. 76.↵
    1. Müller FO,
    2. Hundt HK,
    3. Luus HG,
    4. van Dyk M,
    5. et al.
    (1987) Comparative bio-availability of theophylline whole and halved sustained-release tablets. S Afr Med J 72 (3):175–178, pmid:3299763.
    OpenUrlPubMed
  77. 77.↵
    1. Mosena MS,
    2. Van Der Merwe E
    (2009) The appropriateness and risks of tablet splitting. SA Pharmaceutical Journal 76 (7):30–36.
    OpenUrl
  78. 78.↵
    1. Moreland TA,
    2. McMurdo MET,
    3. McEwen J
    (1989) Multiple dose comparison of a whole 240 mg verapamil sustained-release tablet with two half tablets. Biopharm Drug Dispos 10 (3):311–319, doi:10.1002/bdd.2510100309.
    OpenUrlCrossRefPubMed
  79. 79.↵
    1. McDevitt JT,
    2. Gurst AH,
    3. Chen Y
    (1998) Accuracy of tablet splitting. Pharmacotherapy 18 (1):193–197, pmid:9469693.
    OpenUrlPubMed
  80. 80.
    1. Matuschka PR,
    2. Graves JB
    (2001) Mean dose after splitting sertraline tablets. J Clin Psychiatry 62 (10), doi:10.4088/jcp.v62n1012a, pmid:11816873. 826.
    OpenUrlCrossRefPubMed
  81. 81.↵
    1. Mascarenhas Starling F,
    2. Medeiros-Souza P,
    3. Francisco de Camargos E,
    4. et al.
    (2015) Tablet splitting of psychotropic drugs for patients with dementia: a pharmacoepidemiologic study in a brazilian sample. Clin Ther 37 (10):2332–2338, doi:10.1016/j.clinthera.2015.08.015, pmid:26383240.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Marriott JL,
    2. Nation RL
    (2002) Splitting tablets. Aust Prescr 25 (6):133–135, doi:10.18773/austprescr.2002.131.
    OpenUrlCrossRef
  83. 83.↵
    1. Margiocco ML,
    2. Warren J,
    3. Borgarelli M,
    4. Kukanich B
    (2009) Analysis of weight uniformity, content uniformity and 30-day stability in halves and quarters of routinely prescribed cardiovascular medications. J Vet Cardiol 11 (1):31–39, doi:10.1016/j.jvc.2009.04.003, pmid:19477704.
    OpenUrlCrossRefPubMed
  84. 84.↵
    1. Mandal TK
    (1996) Effect of tablet integrity on the dissolution rate of sustained-release preparations. J Clin Pharm Ther 21 (3):155–157, doi:10.1111/j.1365-2710.1996.tb00015.x.
    OpenUrlCrossRefPubMed
  85. 85.
    1. Lee VWY,
    2. Yu Y,
    3. Tang L,
    4. Yan B
    (2013) Impact of pill-splitting training on drug physiochemical properties, compliance and clinical outcomes in elderly population: A cross-over cohort study. Value Health 16 (7), doi:10.1016/j.jval.2013.08.1211. A514.
    OpenUrlCrossRef
  86. 86.
    1. Kumari S,
    2. Pathak K
    (2013) Tablet splitting - managed care pharmacy. Pharma Times 45 (6):9–12.
    OpenUrl
  87. 87.
    1. Kadi AA,
    2. Abdelhameed AS,
    3. Attwa MW,
    4. et al.
    (2016) Liquid chromatographic-mass spectrometric method for determination of drug content uniformity of two commonly used dermatology medications in a split-tablet dosage form. Trop J Pharm Res 15 (6):1283, doi:10.4314/tjpr.v15i6.22.
    OpenUrlCrossRef
  88. 88.↵
    1. Jonkman JH,
    2. van der Boon WJ,
    3. Schoenmaker R,
    4. et al.
    (1984) The absolute bioavailability of a new pediatric sustained release theophylline tablet, when given as whole or divided tablets. Int J Clin Pharmacol Ther Toxicol 22 (9):506–510.
    OpenUrlPubMed
  89. 89.↵
    1. Isbera M,
    2. Abbood A,
    3. Ibrahim W
    (2016) Weight and content uniformity of warfarin sodium half tablets. Res J Pharm Technol 9 (3):215–218, doi:10.5958/0974-360X.2016.00039.1.
    OpenUrlCrossRef
  90. 90.↵
    1. Hsu C-C,
    2. Chou C-Y,
    3. Chou C-L,
    4. et al.
    (2014) Impact of a warning CPOE system on the inappropriate pill splitting of prescribed medications in outpatients. PloS One 9 (12), doi:10.1371/journal.pone.0114359, pmid:25479360. e114359.
    OpenUrlCrossRefPubMed
  91. 91.↵
    1. Hill SW,
    2. Varker AS,
    3. Karlage K,
    4. Myrdal PB
    (2009) Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications. J Manag Care Pharm 15 (3):253–261, doi:10.18553/jmcp.2009.15.3.253, pmid:19326956.
    OpenUrlCrossRefPubMed
  92. 92.↵
    1. Helmy SA
    (2015) Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting. J Manag Care Spec Pharm 21 (1):76–86, doi:10.18553/jmcp.2015.21.1.76, pmid:25562775.
    OpenUrlCrossRefPubMed
  93. 93.↵
    1. Habib WA,
    2. Alanizi AS,
    3. Abdelhamid MM,
    4. Alanizi FK
    (2014) Accuracy of tablet splitting: comparison study between hand splitting and tablet cutter. Saudi Pharm J 22 (5):454–459, doi:10.1016/j.jsps.2013.12.014, pmid:25473334.
    OpenUrlCrossRefPubMed
  94. 94.
    1. Gupta A,
    2. Hunt RL,
    3. Khan MA
    (2008) Influence of tablet characteristics on weight variability and weight loss in split tablets. Am J Health Syst Pharm 65 (24):2326–2328, doi:10.2146/ajhp080371, pmid:19052274.
    OpenUrlFREE Full Text
  95. 95.↵
    1. Grissinger M
    (2010) Tablet splitting—only if you “half” to. P T 35 (2):69–70.
    OpenUrl
  96. 96.↵
    1. Greene HL
    (2000) After being prescribed a medication to which I was unusually sensitive, my doctor told me to take half a pill. is it safe to split pills? Health News 6 (9). 10.
  97. 97.↵
    1. Gee M,
    2. Hasson NK,
    3. Hahn T,
    4. Ryono R
    (2002) Effects of a tablet-splitting program in patients taking HMG-coa reductase inhibitors: analysis of clinical effects, patient satisfaction, compliance, and cost avoidance. J Manag Care Pharm 8 (6):453–458, doi:10.18553/jmcp.2002.8.6.453.
    OpenUrlCrossRefPubMed
  98. 98.↵
    1. Freeman MK,
    2. White W,
    3. Iranikhah M
    (2012) Tablet splitting: a review of weight and content uniformity. Consult Pharm 27 (5):341–352, doi:10.4140/TCP.n.2012.341.
    OpenUrlCrossRefPubMed
  99. 99.↵
    1. Freeman MK,
    2. White W,
    3. Iranikhah M
    (2012) Tablet splitting: a review of the clinical and economic outcomes and patient acceptance. Second of a 2-part series. Part 1 was published in May 2012 (Consult Pharm 2012;27:239-53). Consult Pharm 27 (6):421–430, doi:10.4140/TCP.n.2012.421.
    OpenUrlCrossRefPubMed
  100. 100.
    1. Fischbach MS,
    2. Gold JL,
    3. Lee M,
    4. et al.
    (2001) Pill-splitting in a long-term care facility. CMAJ 164 (6):785–786, pmid:11276544.
    OpenUrlFREE Full Text
  101. 101.↵
    1. Fawell NG,
    2. Cookson TL,
    3. Scranton SS
    (1999) Relationship between tablet splitting and compliance, drug acquisition cost, and patient acceptance. Am J Health Syst Pharm 56 (24):2542–2545, doi:10.1093/ajhp/56.24.2542.
    OpenUrlAbstract/FREE Full Text
  102. 102.↵
    1. Fagerström PO
    (1980) Pharmacokinetics of whole and half theo-dur tablets. Eur J Respir Dis Suppl 109 62–66, pmid:6934089.
    OpenUrlPubMed
  103. 103.↵
    1. Eserian JK,
    2. Lombardo M,
    3. Chagas JR,
    4. Galduróz JCF
    (2018) Actual versus expected doses of half tablets containing prescribed psychoactive substances: A systematic review. Prim Care Companion CNS Disord 20 (1), doi:10.4088/PCC.17r02211, pmid:29469240. 17r02211.
    OpenUrlCrossRefPubMed
  104. 104.
    1. Erramouspe J,
    2. Jarvi EJ
    (1997) Effect on dissolution from halving methylphenidate extended-release tablets. Ann Pharmacother 31 (10):1123–1126, doi:10.1177/106002809703101001, pmid:9337434.
    OpenUrlCrossRefPubMed
  105. 105.↵
    1. Elliott I,
    2. Mayxay M,
    3. Yeuichaixong S,
    4. et al.
    (2014) The practice and clinical implications of tablet splitting in international health. Tropical Medicine & International Health 19 (7):754–760, doi:10.1111/tmi.12309, pmid:24702766.
    OpenUrlCrossRefPubMed
  106. 106.
    1. Dosti B,
    2. Malaj L,
    3. Xhafaj D
    (2016) Statistic estimation of breaking tablets of enalapril 20 mg. International Journal of Pharmacy and Pharmaceutical Sciences 8 (6):222–224.
    OpenUrl
  107. 107.↵
    1. Dormuth CR,
    2. Schneeweiss S,
    3. Brookhart AM,
    4. et al.
    (2008) Frequency and predictors of tablet splitting in statin prescriptions: a population-based analysis. Open Med 2 (3):e74–e82, pmid:21602952.
    OpenUrlPubMed
  108. 108.↵
    1. Donkerbroek L,
    2. Van Riet-Nales D,
    3. Agnes N,
    4. et al.
    (2016) DI-079 developing a test battery for people’s hand-eye function in relation to tablet subdivision. European Journal of Hospital Pharmacy 23 (Suppl 1), doi:10.1136/ejhpharm-2016-000875.345. A153.
    OpenUrlCrossRef
  109. 109.
    1. De Spiegeleer B,
    2. Van Bortel L,
    3. Castelein P,
    4. et al.
    (2009) The paradox of scored tablets: a cost-saving risk. Pharmazie 64 (8):550–552, doi:10.1691/ph.2009.9532.
    OpenUrlCrossRefPubMed
  110. 110.↵
    1. Cook TJ,
    2. Edwards S,
    3. Gyemah C,
    4. et al.
    (2004) Variability in tablet fragment weights when splitting unscored cyclobenzaprine 10 mg tablets. J Am Pharm Assoc (2003) 44 (5):583–586, doi:10.1331/1544-3191.44.5.583.cook, pmid:15496044.
    OpenUrlCrossRefPubMed
  111. 111.
    1. Cohen CI
    (2003) Regional considerations in the splitting of tablets. Drugs Ther Perspect 19 (7):24–25.
    OpenUrl
  112. 112.↵
    1. Cohen CI,
    2. Cohen SI
    (2002) Potential savings from splitting newer antidepressant medications. CNS Drugs 16 (5):353–358, doi:10.2165/00023210-200216050-00007, pmid:11994024.
    OpenUrlCrossRefPubMed
  113. 113.↵
    1. Chua HM,
    2. Hauet Richer N,
    3. Swedrowska M,
    4. et al.
    (2016) Dissolution of intact, divided and crushed circadin tablets: prolonged vs. immediate release of melatonin. Pharmaceutics 8 (1), doi:10.3390/pharmaceutics8010002. 2.
    OpenUrlCrossRef
  114. 114.
    1. Chou C-Y,
    2. Hsu C-C,
    3. Chiang S-C,
    4. et al.
    (2013) Association between physician specialty and risk of prescribing inappropriate pill splitting. PloS One 8 (7), doi:10.1371/journal.pone.0070113, pmid:23922926. e70113.
    OpenUrlCrossRefPubMed
  115. 115.
    1. Chou C-L,
    2. Hsu C-C,
    3. Chou C-Y,
    4. et al.
    (2015) Tablet splitting of narrow therapeutic index drugs: a nationwide survey in taiwan. Int J Clin Pharm 37 (6):1235–1241, doi:10.1007/s11096-015-0194-0, pmid:26399507.
    OpenUrlCrossRefPubMed
  116. 116.↵
    1. Costa P,
    2. Sousa Lobo JM
    (2001) Divisability of diltiazem matrix sustained-release tablets. Pharm Dev Technol 6 (3):343–351, doi:10.1081/pdt-100002616.
    OpenUrlCrossRefPubMed
  117. 117.↵
    1. Costa P,
    2. Amaral H,
    3. Sousa Lobo JM
    (2000) Dissolution characteristics of divisible tablets. STPPharma Sciences 10 (5):373–377.
    OpenUrl
  118. 118.↵
    1. Ciavarella AB,
    2. Khan MA,
    3. Gupta A,
    4. Faustino PJ
    (2016) Dose uniformity of scored and unscored tablets: application of the FDA tablet scoring guidance for industry. PDA J Pharm Sci Technol 70 (6):523–532, doi:10.5731/pdajpst.2016.006411, pmid:27974592.
    OpenUrlAbstract/FREE Full Text
  119. 119.
    1. Barends DM,
    2. Groot DW,
    3. van der Steen JC,
    4. et al.
    (2006) Results of a market surveillance study in the netherlands on break-mark tablets. Pharmeur Sci Notes 2006 (2):1–7, pmid:17691208.
    OpenUrlPubMed
  120. 120.↵
    1. Barends DM,
    2. Groot DW,
    3. Frijlink HW,
    4. et al.
    (2005) Development of an in vivo test procedure for the ease of breaking of scored tablets. Pharmeur Sci Notes 2005 (1):27–30, pmid:17687891.
    OpenUrlPubMed
  121. 121.↵
    1. Bachynsky J,
    2. Wiens C,
    3. Melnychuk K
    (2002) The practice of splitting tablets: cost and therapeutic aspects. Pharmacoeconomics 20 (5):339–346, doi:10.2165/00019053-200220050-00005, pmid:11994043.
    OpenUrlCrossRefPubMed
  122. 122.↵
    1. Arnet I,
    2. Hersberger KE
    (2010) Misleading score-lines on tablets: facilitated intake or fractional dosing? Swiss Med Wkly 140 (7–8):105–110, pmid:20069474.
    OpenUrlPubMed
  123. 123.
    1. Baruch L,
    2. Gupta B,
    3. Lieberman-Blum SS,
    4. et al.
    (2008) Ezetimibe 5 and 10 mg for lowering LDL-C: potential billion-dollar savings with improved tolerability. Am J Manag Care 14 (10):637–641, pmid:18837641.
    OpenUrlPubMed
  124. 124.↵
    1. Berg C,
    2. Ekedahl A
    (2010) Dosages involving splitting tablets: common but unnecessary? J Pharm Health Serv Res 1 (3):137–141, doi:10.1111/j.1759-8893.2010.00020.x. http://doi.wiley.com/10.1111/jphs.2010.1.issue-3.
    OpenUrlCrossRef
  125. 125.↵
    1. Abu-Geras D,
    2. Hadziomerovic D,
    3. Leau A,
    4. et al.
    (2017) Accuracy of tablet splitting and liquid measurements: an examination of who, what and how. J Pharm Pharmacol 69 (5):603–612, doi:10.1111/jphp.12671, pmid:28028813.
    OpenUrlCrossRefPubMed
  126. 126.
    1. Brown K,
    2. Thomas D,
    3. McKenney K,
    4. et al.
    (2019) Impact of splitting or crushing on the relative bioavailability of the darunavir/cobicistat/emtricitabine/tenofovir alafenamide single-tablet regimen. Clin Pharmacol Drug Dev 8 (4):541–548, doi:10.1002/cpdd.632, pmid:30508308.
    OpenUrlCrossRefPubMed
  127. 127.↵
    1. Biron C,
    2. Licznar P,
    3. Hansel S,
    4. Schved JF
    (1999) Oral anticoagulant drugs: do not cut tablets in quarters. Thromb Haemost 82 (3), doi:10.1055/s-0037-1614356, pmid:10494792. 1201.
    OpenUrlCrossRefPubMed
  128. 128.↵
    1. Allemann SS,
    2. Bornand D,
    3. Hug B,
    4. et al.
    (2015) Issues around the prescription of half tablets in northern switzerland: the irrational case of quetiapine. Biomed Res Int 2015 doi:10.1155/2015/602021, pmid:26539514. 602021.
    OpenUrlCrossRefPubMed
  129. 129.
    1. Caldwell SM,
    2. Raitt JR
    (2010) Oral medication administration: implications caused by capsule splitting. J Am Pharm Assoc (2003) 50 (4):532–533, doi:10.1331/JAPhA.2010.08079.
    OpenUrlCrossRef
  130. 130.
    1. Doeve M,
    2. Van Den Bemt B,
    3. Van Riet Dales D,
    4. et al.
    (2013) Not all commercially available splitting devices are sufficiently accurate and precise to use in clinical practice. in: 42nd ESCP symposium on clinical pharmacy: implementation of pharmacy practice; prague, czech republic, 16-18 october 2013. Int J Clin Pharm 35 (6), doi:10.1007/s11096-013-9886-5. 1276.
    OpenUrlCrossRef
  131. 131.
    1. El-Baseir M,
    2. Bsir HEL
    (2012) Evaluation of split tablets of cardiovascular medicines. in: abstracts of the royal pharmaceutical society (RPS) annual conference 2012, 9–10 september 2012, birmingham, UK. Int J Pharm Pract 20 (Supplement_2):46–47, doi:10.1111/j.2042-7174.2012.00235.x.
    OpenUrlCrossRef
  132. 132.
    1. El-Baseir M,
    2. El-Basir H
    (2013) Divisibility of tablets using different splitter models. in: research posters. Int J Pharm Pract 21 (Supplement_2):107–108, doi:10.1111/ijpp.12064.
    OpenUrlCrossRef
  133. 133.↵
    1. Gharaibeh SF,
    2. Tahaineh LM,
    3. Khasawneh AH
    (2018) Tablet splitting practice in jordan. J Pharm Health Serv Res 9 (4):373–379, doi:10.1111/jphs.12258. http://doi.wiley.com/10.1111/jphs.2018.9.issue-4.
    OpenUrlCrossRef
  134. 134.↵
    1. Gracia-Vásquez SL,
    2. González-Barranco P,
    3. Gracia-Vásquez YA,
    4. et al.
    (2017) Tablet splitting of commonly used mexican medications in the outpatient setting. Lat Am J Pharm 36 (8):1688–1694.
    OpenUrl
  135. 135.↵
    1. Notenboom K,
    2. Vromans H,
    3. Leufkens H,
    4. Bouvy M
    (2016) Can older people break scored tablets by hand? in: 44th ESCP international symposium on clinical pharmacy medicines information: making better decisions lisbon, portugal, 28–30 october 2015. Journal of Clinical Pharmacy 38 (2), doi:10.1007/s11096-015-0240-y. 510.
    OpenUrlCrossRef
  136. 136.
    1. Rahmouni M,
    2. Larin CG,
    3. Kojoian L-M,
    4. et al.
    (2017) Influence of physical factors on quality attribute of scored tablets. In: conference 2017: from innovation to patient solution. An international symposium held jointly by CSPS and CC-CRS, may 10-12, 2017, Montréal, QC Canada. Journal of Pharmacy & Pharmaceutical Sciences 20 doi:10.18433/J3P36G. s121.
    OpenUrlCrossRef
  137. 137.↵
    (2003) The usefulness of splitting tablets as a cost-saving strategy is limited. Drugs & Therapy Perspectives 19 (7):21–25, doi:10.2165/00042310-200319070-00008.
    OpenUrlCrossRef
  138. 138.↵
    (2011) Use a splitting device when tablets need to be split. Australian Journal of Pharmacy 92 (1093):84.
    OpenUrl
  139. 139.↵
    1. Atkin PA,
    2. Finnegan TP,
    3. Ogle SJ,
    4. Shenfield GM
    (1994) Functional ability of patients to manage medication packaging: a survey of geriatric inpatients. Age Ageing 23 (2):113–116, doi:10.1093/ageing/23.2.113, pmid:8023717.
    OpenUrlCrossRefPubMed
  140. 140.↵
    1. Mehuys E,
    2. Dupond L,
    3. Petrovic M,
    4. et al.
    (2012) Medication management among home-dwelling older patients with chronic diseases: possible roles for community pharmacists. J Nutr Health Aging 16 (8):721–726, doi:10.1007/s12603-012-0028-x, pmid:23076515.
    OpenUrlCrossRefPubMed
  141. 141.↵
    1. Denneboom W,
    2. Dautzenberg MGH,
    3. Grol R,
    4. De Smet P
    (2005) User-related pharmaceutical care problems and factors affecting them: the importance of clinical relevance. J Clin Pharm Ther 30 (3):215–223, doi:10.1111/j.1365-2710.2005.00636.x, pmid:15896238.
    OpenUrlCrossRefPubMed
  142. 142.↵
    1. Wilson MG,
    2. Kaiser FE,
    3. Morley JE
    (2001) Tablet-breaking ability of older persons with type 2 diabetes mellitus. Diabetes Educ 27 (4):530–540, doi:10.1177/014572170102700408, pmid:12212341.
    OpenUrlCrossRefPubMed
  143. 143.↵
    1. Carr-Lopez SM,
    2. Mallett MS,
    3. Morse T
    (1995) The tablet splitter: barrier to compliance or cost-saving instrument? Am J Health Syst Pharm 52 (23):2707–2708, doi:10.1093/ajhp/52.23.2707, pmid:8601268.
    OpenUrlCrossRefPubMed
  144. 144.↵
    1. Van Riet-Nales D,
    2. Donkerbroek L,
    3. Nicia A,
    4. et al.
    (2020) The development of a test battery to assess the hand-eye functions relevant in predicting easy and accurate tablet subdivision in older people: a pilot study. Br J Clin Pharmacol 86 (10):1969–1981, doi:10.1111/bcp.14201, pmid:31875976.
    OpenUrlCrossRefPubMed
  145. 145.↵
    1. Gupta P,
    2. Gupta K
    (1988) Broken tablets: does the sum of the parts equal the whole? Am J Hosp Pharm 45 (7), doi:10.1093/ajhp/45.7.1498, pmid:3414713. 1498.
    OpenUrlCrossRefPubMed
  146. 146.↵
    1. Mylrea M,
    2. Robertson S,
    3. Haywood A,
    4. Glass B
    (2012) Stability of dispersible aspirin tablets repacked into dosette boxes. J Pharm Pract Res 42 (3):204–207, doi:10.1002/j.2055-2335.2012.tb00171.x.
    OpenUrlCrossRef
  147. 147.↵
    1. Seong S,
    2. Shin J-Y,
    3. Kim D,
    4. et al.
    (2019) The effect of tablet splitting on the mass loss, uniformity, and stability: by hand or splitter? JAASP 8 7–14. https://www.aaspjournal.org/uploads/155/6207_pdf.pdf.
    OpenUrl
  148. 148.↵
    1. De Baerdemaeker LE,
    2. Mortier EP,
    3. Struys MM
    (2004) Pharmacokinetics in obese patients. CEACCP 4 (5):152–155, doi:10.1093/bjaceaccp/mkh042.
    OpenUrlCrossRef
  149. 149.↵
    1. Duncan MC,
    2. Castle SS,
    3. Streetman DS
    (2002) Effect of tablet splitting on serum cholesterol concentrations. Ann Pharmacother 36 (2):205–209, doi:10.1345/aph.1A233, pmid:11847935.
    OpenUrlCrossRefPubMed
  150. 150.↵
    1. Borja-Oliveira C de
    (2013) Pill organizers and pill cutters: risks and limitations. Rev Saude Publica 47 (1):123–127, doi:10.1590/s0034-89102013000100016, pmid:23703138.
    OpenUrlCrossRefPubMed
  151. 151.↵
    1. Duman E,
    2. Yuksel N,
    3. Olin B,
    4. Sakr A
    (2000) Effect of scoring design on the uniformity of extended release matrix tablet halves. Pharmazeutische Industrie 62 (7):547–550.
    OpenUrl
  152. 152.↵
    1. Therapeutics Initiative
    (2020) Special Edition: March 2020 Pill splitting: making the most of meds in a time of need. accessed. https://www.ti.ubc.ca/2020/03/23/special-edition-march-2020-pill-splitting. 27 Apr 2022.
Back to top
Previous ArticleNext Article

In this issue

BJGP Open
Vol. 6, Issue 3
September 2022
  • Table of Contents
  • Index by author
Download PDF
Download PowerPoint
Email Article

Thank you for recommending BJGP Open.

NOTE: We only request your email address so that the person to whom you are recommending the page knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Concerns regarding tablet splitting: a systematic review
(Your Name) has forwarded a page to you from BJGP Open
(Your Name) thought you would like to see this page from BJGP Open.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Concerns regarding tablet splitting: a systematic review
Aanchal K Saran, Natalie A Holden, Scott R Garrison
BJGP Open 2022; 6 (3): BJGPO.2022.0001. DOI: 10.3399/BJGPO.2022.0001

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Concerns regarding tablet splitting: a systematic review
Aanchal K Saran, Natalie A Holden, Scott R Garrison
BJGP Open 2022; 6 (3): BJGPO.2022.0001. DOI: 10.3399/BJGPO.2022.0001
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
  • Mendeley logo Mendeley

Jump to section

  • Top
  • Article
    • Abstract
    • How this fits in
    • Introduction
    • Method
    • Results
    • Discussion
    • Notes
    • References
  • Figures & Data
  • Info
  • eLetters
  • PDF

Keywords

  • cost savings
  • delayed-action preparations
  • dose-reduction
  • geriatric prescribing
  • medication errors
  • pill-splitting
  • tablets

More in this TOC Section

  • General practitioner roles in emergency medical services: a systematic mapping review and narrative synthesis
  • Parental experiences of eczema advice in online parenting forums: Qualitative interview study
  • Characteristics of asthma patients overprescribed short-acting beta-agonist (SABA) reliever inhalers stratified by blood eosinophil count in North East London – a cross-sectional observational study
Show more Research

Related Articles

Cited By...

Intended for Healthcare Professionals

@BJGPOpen's Likes on Twitter

 
 

British Journal of General Practice

NAVIGATE

  • Home
  • Latest articles
  • Authors & reviewers
  • Accessibility statement

RCGP

  • British Journal of General Practice
  • BJGP for RCGP members
  • RCGP eLearning
  • InnovAiT Journal
  • Jobs and careers

MY ACCOUNT

  • RCGP members' login
  • Terms and conditions

NEWS AND UPDATES

  • About BJGP Open
  • Alerts
  • RSS feeds
  • Facebook
  • Twitter

AUTHORS & REVIEWERS

  • Submit an article
  • Writing for BJGP Open: research
  • Writing for BJGP Open: practice & policy
  • BJGP Open editorial process & policies
  • BJGP Open ethical guidelines
  • Peer review for BJGP Open

CUSTOMER SERVICES

  • Advertising
  • Open access licence

CONTRIBUTE

  • BJGP Life
  • eLetters
  • Feedback

CONTACT US

BJGP Open Journal Office
RCGP
30 Euston Square
London NW1 2FB
Tel: +44 (0)20 3188 7400
Email: bjgpopen@rcgp.org.uk

BJGP Open is an editorially-independent publication of the Royal College of General Practitioners

© 2023 BJGP Open

Online ISSN: 2398-3795